Control Of Multidrug-resistant Bacteria Research Articles

Strategies for Prevention and Control of Multidrug-resistant Bacteria in Ruminants

Antibiotics are no longer effective in treating bacterial infections due to antimicrobial drug resistance. Therefore, various alternative strategies have been developed to combat multidrug-resistant (MDR) bacteria. The current review article aimed to shed light on strategies to prevent and control MDR bacteria in ruminants. Due to the development of new resistant bacteria, there is a need for effective treatments and prevention protocols in livestock and humans. With growing antibiotic-resistant organisms, a few antimicrobial medicines will be available to treat the infection when no new drugs are developed. This highlights the importance of looking for other strategies for combating antibiotic-resistant bacteria. In this regard, alternative strategies have been proposed to minimize antimicrobial drug overuse in ruminants. These alternative procedures include alternatives for growth promotion (such as in-feed enzymes, probiotics, prebiotics, synbiotics, and antimicrobial peptides), alternatives for disease prevention (such as vaccines, immune modulators, chicken egg yolk antibodies, farm management, and biosecurity), and alternatives for disease treatment such as plant extracts and phage-therapy to antibiotics. These alternative methods should be safe‎ and efficient without inducing microbial resistance.

Photodynamic inactivation of multidrug-resistant bacteria in wastewater effluent using green phytochemicals as a natural photosensitizer

The control of multidrug-resistant bacteria (MDRB) is a great challenge in the 21st century. Photodynamic treatment (PDT) is one of the promising approaches to control MDRB. In the process, powerful oxidants such as reactive oxygen species (ROS) are produced, which cause cytotoxic damage and cell death of bacteria. This study examined a new and environment-friendly strategy for the photodynamic inactivation of two MDRB (Escherichia coli and Staphylococcus aureus) and total coliform (TC) in wastewater effluent using two phytochemicals, pyrogallol (PGL) and terpinolene (TPN), along with white and blue light-emitting diode (LED) light. Fourier-transform infrared spectroscopy (FTIR) of the phytochemicals confirmed the presence of different phenolic and aromatic compounds, which can enhance the generation of ROS alongside inactivating the bacterial cells. In the PDT process, white LED light was more active in controlling MDRB than blue LED light. After 80 min irradiation with white LED light (17 mW/cm2), the MDRB bacteria were eradicated completely at a minimum inhibitory concentration (MIC) dose (0.156 mg/mL for E. coli and 0.078 mg/mL for S. aureus) of PGL. In addition, light intensity was an important parameter in photodynamic disinfection. The TC in the secondary effluent was inactivated completely by both phytochemicals after 60 min of exposure to white LED light with an intensity of 80 mW/cm2. The photosensitizing activity of phytochemicals was analyzed by a bactericidal and imidazole-RNO assay. These assays showed that PGL contributed to the generation of •OH radicals, whereas TPN produced 1O2 in the PDT process. Transmission electron microscopy (TEM) confirmed bacterial cell disruption after treatment. Overall, PDT using the phytochemicals as PS is a sustainable approach to control the MDRB and TC in wastewater successfully.

Functional comparison of anti-restriction and anti-methylation activities of ArdA, KlcA, and KlcAHS from Klebsiella pneumoniae.

Anti-restriction proteins are typically encoded by plasmids, conjugative transposons, or phages to improve their chances of entering a new bacterial host with a type I DNA restriction and modification (RM) system. The invading DNA is normally destroyed by the RM system. The anti-restriction proteins ArdA, KlcA, and their homologues are usually encoded on plasmid of carbapenemase-resistant Klebsiella pneumoniae. We found that the plasmid sequence and restriction proteins affected horizontal gene transfer, and confirmed the anti-restriction and anti-methylation activities of ArdA and KlcA during transformation and transduction. Among the three anti-restriction proteins, ArdA shows stronger anti-restriction and anti-methylation effects, and KlcAHS was weaker. KlcA shows anti-methylation only during transformation. Understanding the molecular mechanism underlying the clinical dissemination of K. pneumoniae and other clinically resistant strains from the perspective of restrictive and anti-restrictive systems will provide basic theoretical support for the prevention and control of multidrug-resistant bacteria, and new strategies for delaying or even controlling the clinical dissemination of resistant strains in the future.

In Vitro Evaluation of a Phage Cocktail Controlling Infections with Escherichia coli.

Worldwide, poultry industry suffers from infections caused by avian pathogenic Escherichia coli. Therapeutic failure due to resistant bacteria is of increasing concern and poses a threat to human and animal health. This causes a high demand to find alternatives to fight bacterial infections in animal farming. Bacteriophages are being especially considered for the control of multi-drug resistant bacteria due to their high specificity and lack of serious side effects. Therefore, the study aimed on characterizing phages and composing a phage cocktail suitable for the prevention of infections with E. coli. Six phages were isolated or selected from our collections and characterized individually and in combination with regard to host range, stability, reproduction, and efficacy in vitro. The cocktail consisting of six phages was able to inhibit formation of biofilms by some E. coli strains but not by all. Phage-resistant variants arose when bacterial cells were challenged with a single phage but not when challenged by a combination of four or six phages. Resistant variants arising showed changes in carbon metabolism and/or motility. Genomic comparison of wild type and phage-resistant mutant E28.G28R3 revealed a deletion of several genes putatively involved in phage adsorption and infection.

Colonization of Resistant Microorganisms in Renal Transplants

Background: Kidney transplant recipients are a group of patients at risk for healthcare-related infections. The results of this study make an important clinical contribution and contribute to findings options to decrease the infection-related morbidity and mortality that affects this patient population. Objectives: We evaluated the prevalence of colonization by multidrug-resistant bacteria, Klebsiella pneumoniae carbapenemase (KPC)–producing bacteria, vancomycin-resistant enterococci (VRE), and methicillin-resistant Staphylococcus aureus (MRSA) in renal transplant patients; we identified the infection rate, morbidity, and mortality in this population. Methods: Prospective cohort study was conducted at the Kidney and Hypertension Hospital from 2012 to 2015. This project was approved by the Unifesp Research Ethics Committee (no. 1630/11) and an informed consent form was obtained from patients included in the study. Study protocol: Data collection was performed in 2 phases: within the first 24 hours after transplantation and 7 days after transplantation. For all included patients, the following data were collected: identification data, clinical data, and laboratory tests of the first day in the study. All included patients (colonized or not) were followed prospectively for 6 months or until treatment change or death. Results: The study included 200 renal transplant patients in accordance with the inclusion and exclusion criteria. We observed that 76 (38%) patients included in our sample were colonized; 8% S. aureus, 11% Enterococcus, and 19% K. pneumoniae. We verified the presence of concomitant colonization of 1 or more of these pathogens. The most prevalent concomitance identified in our population was E. coli and K. pneumoniae. We identified the presence of diabetes and diabetes associated with hypertension as risk factor for colonization. Thus, patients with more systemic complications may be at risk for colonization by multidrug-resistant bacteria. Another risk factor for colonization was antibiotic use in the 6 months prior to transplantation. Transplant-related outcomes were length of stay after transplantation, delayed graft function (ie, dialysis after the transplantation) and postoperative care in an intensive care unit. At the 6-month follow-up, we identified urinary infection and surgical site infection as risk factors. One death occurred due to stroke in the group of colonized patients, unrelated to infectious causes. Conclusions: These results show fundamental aspects for health professionals for bacterial characterization, transmission, and resistance mechanisms and, mainly, tools for prevention and control of multidrug-resistant bacteria from patients colonized under conservative treatment before the complexity of high-risk procedures begins, such as dialysis and transplantation to reduce morbidity and mortality.Funding: FAPESP São Paulo Research Support FoundationDisclosures: None

Prevention and Control of Multidrug-Resistant Bacteria in The Netherlands and Germany-The Impact of Healthcare Structures.

The Netherlands and Germany are neighbouring countries within the European Union but are differently affected by multidrug-resistant microorganisms (MDRO). In this narrative review, we summarize data about antibiotic use, the occurrence of MDRO and healthcare-associated infections in these two countries, as well as data about organizational and structural differences between the Dutch and German healthcare systems. These results are discussed with a focus on whether or how the organization of healthcare influences MDRO prevention. We found that from the point of view of MDRO prevention, a higher density of inpatient care, a higher number of hospitals, a longer length of stay and lower staffing ratios might facilitate MDRO dissemination in German hospitals.

Constructing and deconstructing the bacterial cell wall.

The history of modern medicine cannot be written apart from the history of the antibiotics. Antibiotics are cytotoxic secondary metabolites that are isolated from Nature. The antibacterial antibiotics disproportionately target bacterial protein structure that is distinct from eukaryotic protein structure, notably within the ribosome and within the pathways for bacterial cell-wall biosynthesis (for which there is not a eukaryotic counterpart). This review focuses on a pre-eminent class of antibiotics-the β-lactams, exemplified by the penicillins and cephalosporins-from the perspective of the evolving mechanisms for bacterial resistance. The mechanism of action of the β-lactams is bacterial cell-wall destruction. In the monoderm (single membrane, Gram-positive staining) pathogen Staphylococcus aureus the dominant resistance mechanism is expression of a β-lactam-unreactive transpeptidase enzyme that functions in cell-wall construction. In the diderm (dual membrane, Gram-negative staining) pathogen Pseudomonas aeruginosa a dominant resistance mechanism (among several) is expression of a hydrolytic enzyme that destroys the critical β-lactam ring of the antibiotic. The key sensing mechanism used by P. aeruginosa is monitoring the molecular difference between cell-wall construction and cell-wall deconstruction. In both bacteria, the resistance pathways are manifested only when the bacteria detect the presence of β-lactams. This review summarizes how the β-lactams are sensed and how the resistance mechanisms are manifested, with the expectation that preventing these processes will be critical to future chemotherapeutic control of multidrug resistant bacteria.

Strategies to control antibiotic resistance: results from a survey in Italian children's hospitals.

Antimicrobial stewardship programs and comprehensive infection control programs represent the main strategies to limit the emergence and transmission of multi-drug resistant bacteria in hospital settings. The purpose of this study was to describe strategies implemented in Italian children's hospitals for controlling antibiotic resistance. Cross sectional multicenter study. Four tertiary care Italian children's hospitals were invited to participate in a survey aimed at collecting information on activities implemented as of December 2015 using a self-administered online questionnaire. The questionnaire was divided in three sections focalizing on: i) policies for prevention and control of hospital-acquired infection, ii) prevention and control of multi-drug resistant bacteria, and iii) antibiotic prescribing policies and Antimicrobial stewardship programs. Questionnaires were compiled between May and July 2016. All hospitals had multidisciplinary infection control committee, procedures on hand hygiene, isolation measures, disinfection/sterilization, waste disposal and prevention on infections associated to invasive procedures. All sites screened patients for multi-drug resistant bacteria colonization in selected units, and adopted contact precautions for colonized patients. Screening during hospitalization, or in case of infections in the same ward were not universally implemented. All hospitals had policies on surgical prophylaxis, while policies on medical prophylaxis and treatment of bacterial infections varied among sites. Two sites recommended to review the appropriateness of antibiotic prescribing after 48-72 hours and one recommended de-escalation therapy. This study highlighted several areas of improvement, such as actions for screening patients in case of occurrence of multi-drug resistant bacteria, antimicrobial stewardship programs and implementation of policies targeting antibiotic prescriptions for therapeutic purposes and medical prophylaxis.

The novel cathelicidin of naked mole rats, Hg-CATH, showed potent antimicrobial activity and low cytotoxicity

We performed the in silico genome-wide identification of antimicrobial peptides against the available genome sequence of the naked mole rat Heterocephalus glaber (H. glaber). Our results showed the presence of Hg-CATH, the single cathelicidin containing the antimicrobial domain in H. glaber. We chemically synthesized a 25 amino-acid peptide (ΔHg-CATH) corresponding to the predicted antimicrobial-active core region of Hg-CATH, and evaluated its antibacterial activity against seven bacterial strains. The ΔHg-CATH peptide exhibited strong bactericidal activity against gram-negative bacteria, including a multi-drug resistant strain, while showing low toxicity towards mammalian cells, including erythrocytes. Scanning electron microscopy images of bacterial cells treated with ΔHg-CATH showed disruption of their membranes due to the formation of toroidal pores. Identifying novel antimicrobial peptides, such as Hg-CATH, may be important for identifying candidate peptides for the control of multi-drug resistant bacteria.

Molecular identification and screening of mushrooms for antibacterial property against Pseudomonas aeruginosa and Staphylococcus aureus

In this study, 18 mushrooms were collected from Gandhi Krishi Vigyana Kendra (GKVK) campus, University of Agricultural Sciences, Bangalore (India) and identified by Internal Transcribed Spacer (ITS) region using National Centre for Biotechnology Information (NCBI) data base and screened for antibacterial property against two skin infection causing bacteria viz.,Pseudomonas aeruginosa and Staphylococcus aureus in dogs. Eleven mushrooms extract inhibited both the bacteria showing their antimicrobials as broad spectrum while inhibiting gram positive as well as gram negative bacteria. The highest zone of inhibition was recorded from the extract of Lyophyllum sp. The extract of two mushrooms viz., Phlebopus portentosus and Termitomyces sp. inhibited only P. aeruginosa, a gram negative bacterium and the extract of three mushrooms viz., Agaricus sp, Coprinellus disseminates and Agaricus blazei inhibited only S. aureus, a gram positive bacterium, suggesting spectral specificity of their antimicrobial compounds. However, the extracts of two mushrooms viz.,Macrocybe gigantea and Schizophyllum commune did not show inhibition of any of the pathogens. Hence, this study suggests that the occurrence of potential pharmaceuticals in mushrooms can be exploited for control of multidrug resistant bacteria.

Biopolymer zein-coated gold nanoparticles: Synthesis, antibacterial potential, toxicity and histopathological effects against the Zika virus vector Aedes aegypti

The control of multidrug-resistant bacteria as well as insect pests and vectors is timely and important now a days. The present study was designed to evaluate the in vitro antibacterial, antibiofilm and mosquito larvicidal effects of gold nanoparticles synthesized using the zein biopolymer (Ze-AuNPs) against Gram positive (Bacillus pumilus and Bacillus subtilis), Gram negative (Shigella sonnei and Pseudomonas aeruginosa) bacteria and third instar larvae of the dengue and Zika virus vector Aedes aegypti. The synthesized Ze-AuNPs were characterized by UV–vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The antibacterial assays testing Ze-AuNPs at 100μg/ml showed that the zones of inhibition against Gram positive species B. pumilus and B. subtilis were 13.9 and 14.2mm, respectively, while for Gram negative S. sonnei and P. aeruginosa they were 18.1 and 18.4mm, respectively. Light and confocal laser scanning microscopy (CLSM) confirmed the interruption and disintegration of bacterial biofilm post-treatment with Ze-AuNPs at 100μg/ml. In larvicidal assays on A. aegypti, HAuCl4 and Ze-AuNPs treated third instar larvae of A. aegypti showed LC50 of 26.6 and 6.81mg/L, respectively, and LC90 of 81.1 and 13.6mg/L respectively. The histopathological analysis of A. aegypti treated with Ze-AuNPs showed complete disintegration of abdominal region, particularly the midgut and caeca, with loss of lateral and caudal hairs. The stereomicroscopic visualization of A. aegypti treated with Ze-AuNPs showed the loss of upper head hair, lower head hair, antenna hair, lateral hair and caudal hair. Overall, the study concludes that Ze-AuNPs have excellent antibacterial, antibiofilm effects and has ability to control the larval populations of A. aegypti mosquitoes.

β-lactamase-producing Gram-negative bacteria in an intensive care unit in southern Brazil

The present study evaluated the antimicrobial susceptibility profile, β-lactamase production, and genetic diversity of Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. using phenotypic identification, antimicrobial susceptibility testing, and β-lactamase phenotypic detection. Isolates were obtained from patients in an intensive care unit in a hospital in southern Brazil. Bacterial genomic DNA was extracted, followed by the genotypic detection of carbapenemases and enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR). Fifty-six isolates (26 Klebsiella pneumoniae, five Escherichia coli, three Enterobacter aerogenes, nine P. aeruginosa, and 13 Acinetobacter spp.) were evaluated. The phenotypic extended spectrum β-lactamase (ESBL) test was positive in 53.8% of the K. pneumoniae isolates, 100.0% of the E. coli isolates, and 100.0% of the E. aerogenes isolates. Phenotypic and genotypic testing of K. pneumoniae carbapenemase (KPC) was positive in 50.0% of the K. pneumoniae isolates. Phenotypic and genotypic testing showed that none of the P. aeruginosa or Acinetobacter spp. isolates were positive for metallo- β-lactamase (MBL). The bla OXA gene was detected only in Acinetobacter spp. The lowest genetic diversity, determined by ERIC-PCR, was observed among the KPC-producing K. pneumoniae isolates and OXA-producing Acinetobacter spp. isolates, indicating the inadequate dissemination control of multidrug-resistant bacteria in this hospital environment.

Development of antibacterial conjugates using sulfamethoxazole with monocyclic terpenes: A systematic medicinal chemistry based computational approach

Background and objectiveTo develop 6 conjugate agents of the moribund antibiotic sulfamethoxazole (SMZ) joined to 6 individual monoterpenes, followed by protocols of medicinal chemistry as potent antibacterials, against multidrug resistant (MDR) human gruesome pathogenic bacteria. MethodsAntibacterial activities of the proposed conjugates were ascertained by the ‘prediction of activity spectra of substances’ (PASS) program. Drug-likeness parameters and toxicity profiles of conjugates were standardized with the Lipinski rule of five, using cheminformatic tools, Molsoft, molinspiration, OSIRIS and ProTox. Antibacterial activities of individual chemicals and conjugates were examined by targeting the bacterial folic acid biosynthesis enzyme, dihydropteroate synthases (DHPSs) of bacteria, Bacillus anthracis, Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae and Mycobacterium tuberculosis, with 3D structures of DHPSs from protein data bank. ResultsAccording to the PASS program, biological spectral values of conjugate-2, conjugate-5 and conjugate-6 were ascertained effective with ‘probably active’ or ‘Pa’ value > 0.5, for anti-infective and antituberculosic activities. Using molecular docking against 5 cited bacterial DHPSs, effective docking scores of 6 monoterpenes in the specified decreasing order (kcal/mol): −9.72 (eugenol against B. anthracis), −9.61 (eugenol against S. pneumoniae), −9. 42 (safrol, against B. anthracis), −9.39 (thymol, against M. tuberculosis), −9.34 (myristicin, against S. pneumoniae) and −9.29 (thymol, against B. anthracis); whereas the lowest docking score of SMZ was -8.46kcal/mol against S. aureus DHPS. Similarly, effective docking scores of conjugates were as specified (kcal/mol.): −10.80 (conjugate-4 consisting SMZ+safrol, against M. tuberculosis), −10.78 (conjugate-5 consisting SMZ+thymol, against M. tuberculosis), −10.60 (conjugate-5 against B. anthracis), −10.26 (conjugate-2 consisting SMZ+ eugenol, against M. tuberculosis), −10.25 (conjugate-5, against S. aureus) and −10.19 (conjugate-2 against S. pneumoniae. Conjugates-2 and -5 were the most effective antibacterials based on Lipinski rule of five with lethal doses 3471 and 3500mg/kg, respectively and toxicity class levels. ConclusionsConjugate-2 and conjugate-5 were more effective than individual monoterpenes and SMZ, against pathogenic bacteria. Synthesis, characterization and in vitro antibacterial study with acute toxicity testing for Wister rat model of the conjugate-5 could land at success in the recorded computational trial and it could be promoted for synthesis in the control of MDR bacteria.

Analysis and control of multidrug-resistant bacteria in hospital

Analysis and control of multidrug-resistant bacteria in hospital

Analysis and control of multidrug-resistant bacteria in hospital

Objective: To investigate the status of multidrug-resistant bacteria and the prevention and control measures of nosocomial infection in our hospital. Methods: The annual monitoring of multidrug-resistant bacteria infection was measured to summarize the bacteria species, statistical distribution and antibiotic resistance. Identification of multidrug-resistant bacteria infection in patients infected or hospital acquired infections was taken to analyze the reasons of multidrug-resistant bacteria strain and put forward the relevant measures. Results: The top five of multidrug-resistant strains infections were: Gram-positive bacteria including methicillin-resistant Staphylococcus aureus, Staphylococcus aureus ; Gram-negative bacteria including Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae. Conclusions: The occurrence of multidrug-resistant hospital infections could be prevented by rational use of antibiotics, hand hygiene and disinfection management, and reinforced monitoring of multidrug-resistant bacteria.

Application of "net type" management in the prevention and control of multi-drug resistant bacteria

Objective To explore the effect of net type management in the prevention and control of multi-drug resistant organisms(MDROs). Methods Totals of 38 MDROs infected patients were selected from the department of geriatrics psychiatry, neurology and rehabilitation medicine from 2012 to 2013.Totals of 71 cases from January to December 2012 were selected as the control group, and were given the traditional prevention and control management. Totals of 67 cases from January to December 2013 were selected as the experiment group, and were given the net type management. Nosocomial infection, underreporting, implementing prevention and control measures were compared between the two groups. Results The percentages of underreporting, input outside the hospital, nosocomial infection of the experiment group after using the net type management were 5.97%, 39.44% and 43.28%, respectively, those percentages of the control group were 35.21%, 39.44% and 61.97%, and the differences were statistically significant (χ2=16.040, 9.548, 4.108, respectively; P<0.05). The medical orders for separation, setting separation signs, correct use of medical supplies, specific application, material dispose, correct dispose of medical waste and the incidence of health education were 89.55%, 92.54%, 76.12%, 88.06%, 88.06%, 92.54% and 92.54% in the experiment group, which were significantly better than those of the control group (χ2=16.178, 17.646, 39.613, 36.178, 17.006, 30.379, 40.519, respectively; P<0.05). Conclusions The net type management in secondary hospitals is better than the traditional method in the prevention and control of multi-drug resistant bacteria. Key words: Net typemanagement control; Secondary hospital; Multiple drug-resistant organisms; Prevention and control

Control of multidrug resistant bacteria in a tertiary care hospital in India.

BackgroundThe objective of this study was to assess the impact of antimicrobial stewardship programs on the multidrug resistance patterns of bacterial isolates. The study comprised an initial retrospective analysis of multidrug resistance in bacterial isolates for one year (July 2007-June 2008) followed by prospective evaluation of the impact of Antimicrobial Stewardship programs on resistance for two years and nine months (July 2008-March 2011).SettingA 300-bed tertiary care private hospital in Gurgaon, Haryana (India)FindingsMethodsStudy Design• July 2007 to June 2008: Resistance patterns of bacterial isolates were studied.• July 2008: Phase I intervention programme Implementation of an antibiotic policy in the hospital.• July 2008 to June 2010: Assessment of the impact of the Phase I intervention programme.• July 2010 to March 2011: Phase II intervention programme: Formation and effective functioning of the antimicrobial stewardship committee. Statistical correlation of the Defined daily dose (DDD) for prescribed drugs with the antimicrobial resistance of Gram negatives.ResultsPhase I intervention programme (July 2008) resulted in a decrease of 4.47% in ESBLs (E.coli and Klebsiella) and a significant decrease of 40.8% in carbapenem-resistant Pseudomonas. Phase II intervention (July 2010) brought a significant reduction (24.7%) in carbapenem-resistant Pseudomonas. However, the resistance in the other Gram negatives (E.coli, Klebsiella, and Acinetobacter) rose and then stabilized. A positive correlation was observed in Pseudomonas and Acinetobacter with carbapenems and cefoperazone-sulbactam.Piperacillin-tazobactam showed a positive correlation with Acinetobacter only. E.coli and Klebsiella showed positive correlation with cefoparazone-sulbactam and piperacillin-tazobactam.ConclusionAn antimicrobial stewardship programme with sustained and multifaceted efforts is essential to promote the judicious use of antibiotics.